Zinc is present in high concentrations in the mammalian retina. The trace metal apparently has a variety of functions, including serving as an essential constituent in alcohol dehydrogenase, an enzyme vital for regeneration of rhodopsin. Chemical compounds which chelate divalent cations, including at lease one drug in clinical use, have evoked deleterious effects on retinal morphology and function in man and laboratory animals. Our first goals were to examine the effects of acute administration of dithizone and ethambutol on retinal morphology and on physiological measures in vivo and in vitro of retinal function. In Sprague-Dawley rats, frequent intraperitoneal injections of the compounds caused acute changes in the pigment epithelial cells including (depending on drug and dose): opaque inclusion bodies, intracellular disorganization, and autophagic vacuoles. In addition, large doses of dithizone caused photoreceptor degeneration. Electroretinograms in control rats were not different than those recorded from treated rats. On the other hand, mean receptor photocurrents from retinae in vitro were significantly different between the control and treated groups. We propose a series of experiments which would provide basic information about our preliminary results. Our aims are: a) to measure renewal rate of photoreceptor outer segments by light and electron microscopic autoradiography in normal rats vs. rats injected with chelators with or without zinc pretreatment; b) to measure the accumulation rate of radiolabelled products in inclusion bodies and in autophagic vacuoles of the pigment epithelium; c) to study the retinae of rats chronically zinc-deficient to determine if their retinal cell morphology resembles that found after chelator administration. Rats treated with chelating agents prove useful as models for studying pathological processing in retinal dystrophies, and for tests of the effects of metal ion replacement.